Neurodegenerative diseases and injuries of the central nervous system (CMS) - such as Alzheimer's disease, Parkinson's desease, amytrophic leteral sclerosis (ALS), and stroke - disable and kill millions of American's each year, yet there is no cure or even effective treatment for any of these diseases. The discovery of multipotent neural stem cells (NSCs) in adult brain has brought about revolutionary changes in the theory of neurogenesis; however, therapies being developed from embryonic stem cells and NSCs directly isolated from brains are fraught with a number of technical (tumor-/teratoma- genesis, uncontrolled multipotency, sourcing, require immune suppression) and ethical hurdles which have hindered rapid progress toward human therapy. This proposal builds upon the innovative discovery that bone marrow-derived cells (MDCs) cultured in the presence of a specific chemical agent leads to the generation of ACT-N(tm) cells that are capable of migrating and differentiating into new neural and glial cells when implanted into the lateral ventricle of rodent brains. Our long-term goal is to develop ACT-N cells as an effective therapy for patients with debilitating conditions of the CNS including, but not limited to, stroke, Alzheimer's disease, Parkinson's disease, and age-related memory impairment. To achieve this goal, we need to explore the potential ability of ACT-N cells to replace and/or augment the native repair mechanisms that are activated in CNS during disease and/or injury and also to develop robust and reproducible manufacturing strategies with the necessary safety, quality, and process controls. In regards to the latter need, this research plan intends to identify unique characteristics of ACT-N cells that differ from the MDCs from which they are derived, including immunophenotype, DNA methylation levels, and differentiation potential. In addition, initial considerations pertaining to ACT-N safety will be addressed.